PhD Scientific Days 2024

Theoretical and Translational Medicine I.

Hypoxic and Angiogenic Response to Repeated Modulated Electro-Hyperthermia in Murine Triple-Negative Breast Cancer

Text of the abstract

Introduction
Modulated electro-hyperthermia (mEHT) is a novel complementary therapy where a 13.56 MHz radiofrequency current targets cancer cells selectively, inducing tumor damage by thermal and electromagnetic effects. We observed vascular damage in mEHT-treated tumors and investigated the potential synergism between mEHT and inhibition of vasculature recovery in our triple-negative breast cancer (TNBC) model.
Aim
We aimed to investigate effect of repeated mEHT on the vascular and hypoxic profile of TNBC tumors and how digoxin can be repurposed as an anti-cancer drug in combination with mEHT.
Methods
4T1/4T07 isografts were treated three to five times with mEHT. Digoxin was administered daily by intraperitoneal injection to mice in the combination therapy group. Tumor growth was monitored with ultrasound and digital calipers. Tumor destruction histology, blood capillary damage, and molecular changes were detected using immunohistochemistry, flow cytometry, qPCR and western blot.
Results
mEHT induced vascular damage four to twelve hours after treatment leading to tissue hypoxia detected at twenty-four hours. Hypoxia in treated tumors induced an angiogenic recovery twenty-four hours after the last treatment. Administration of the cardiac glycoside digoxin could synergistically augment mEHT-mediated tumor damage and could reduce tissue hypoxia signaling and consequent vascular recovery in mEHT-treated tumors.
Conclusion
Repeated mEHT induced vascular damage and hypoxic stress in TNBC which promoted vascular recovery. Inhibiting this hypoxic stress signaling enhanced the effectiveness of mEHT and may potentially enhance other forms of cancer treatment.